Hemodynamic parameter (hdp) monitoring system for diagnosis of a health condition of a patient

ABSTRACT

A hemodynamic parameter (Hdp) monitoring system for diagnosing a health condition of a patient and for establishing Hdp marker values or Hdp surrogate marker values for purposes of comparison with Hdp values of a patient is provided. An Hdp monitor senses, measures, and records Hdp values exhibited by the patient during a basal or non-exposure period and furthermore Hdp values exhibited by the patient during or after an exposure period during which the patient is exposed to low-energy electromagnetic output signals. An electrically-powered generator is adapted to be actuated to generate said low-energy electromagnetic carrier output signals for exposing or applying to the patient such output signals during said exposure period.

FIELD OF THE INVENTION

This invention relates to a hemodynamic parameter (Hdp) monitoringsystem for diagnosis, more particularly involving a monitor able tosense and monitor various specified Hdp values and providing recordedvalues thereof. The recorded specified Hdp values include valuesrequired for purposes of performing diagnoses in terms of the invention.

BACKGROUND OF THE INVENTION

Various Hdp monitors are available in the art Such monitors aregenerally employed to sense and monitor various Hdp values, usually forpurposes of diagnosing cardiovascular conditions of a patient. Hdpmeasurements performed, generally in conjunction with anelectrocardiogram (ECG), might include measurements of stroke volume(SV), stroke index (SI) and cardiac output (CO). Such measurements areindicated for the diagnosis and therapy of patients suffering fromcardiac conditions such as heart failure, hypertension, coronary arterydisease, pericardial disease, obstructive lung and pleural disease andalso renal insufficiency. So-called impedance cardiography (ICG),involving application of a fixed current (of about 400 microAmps at 40kHz) to spaced apart electrodes is described in the literature forpurposes of measuring actual patient current. This state of the art isessentially concerned with securing CO measurements and comparisons ofthe spaced electrode ICG procedure with well-known and regularlyemployed thermodilution (TD) procedures for measuring CO or calculatingsuch by multiplying stroke volume (SV) with heart-rate (HR).

The state of the art as discussed above has been mentioned in view ofthis involving passage of current to a patient in the ICG procedure,which procedure, however, is concerned only with attempting to secure,as well as is possible, reliable measurements of CO values of patients.Also of some interest from a state of the art perspective, is mention ofdirect digital synthesis (DDS) for ensuring stable current sources,which technology may also, but not necessarily, be employed in acomponent of the hemodynamic monitoring system of the present invention.Further of possible interest from a state of the art perspective, isdisclosure of statistical analyses by means of Band-Altman plots ofdifferences between CO measurements provided by different measurementprocedures. A Bland-Altman plot (Difference plot) is a method of dataplotting used in analyzing the agreement between two different assays,popularized in medical statistics by J. Martin Bland and Douglas G.Altman.

The state of the art as summarized above is to be found in J. Fortin etal./Computers in Biology and Medicine 36 (2006) 1185-1203. This possibleinterest arises from the present invention involving statisticalanalyses and computations related to measurements of a variety ofspecified Hdp values.

Insofar as the present invention is essentially concerned withdiagnosing a health condition of a patient, mention of the state of theart as represented by disclosure comprised in EP Application No. 08 734777.9-1652 related to an electronic system for influencing cellularfunctions in a warm-blooded mammalian subject, where mention is made ofdiagnosis in the following terms: “The electronic system of theinvention is therefore a valuable diagnostic tool for diagnosing thepresence or absence and identities of types of tumor cell growths orcancers”. This disclosure, however, does not contemplate or suggestemploying measured Hdp values as a means for diagnosis of either a typeof cancer or indeed any other form of a health condition of a patient.

In terms of background of the present invention, extensive clinicaltrials performed with the aid of the electronic system described inabove-mentioned EP Application No. 08 734 777.9-1652 led to furtherinvestigations related to effects of treatments performed. These furtherinvestigations included performing multiple measurements of various Hdpvalues in patients and determinations, in terms of the presentinvention, that such values differ dependency of the type of cancer.Such determinations provided basis for proposing a diagnostic procedurebased on measured Hdp values for diagnosing a particular form of cancerharbored by a patient These determinations furthermore suggested thatpractically any form of a poor health condition suffered by a patient,including such conditions as viral, parasitical or other pathogenicinvasions, organ dysfunctions leading to undesirable components such astoxins being comprised in the blood of a patient, drug abuse, poisons,high low-density lipoprotein (LDL) cholesterol levels, venom from asnake-bite and the like, may be diagnosed on the basis of certainidentified measured Hdp values patient's diagnosis. Furthermore, sinceit has previously been determined that Central Nervous System (CNS)disorders described in EP 0 592 851A2, may be successfully treated byapplication to a patient of amplitude modulation (AM) carrier signalsmodulated at predetermined AM frequencies, it is likely that suchconditions may be similarly diagnosed on the basis of certain measuredHdp values. Reference is also made to U.S. Pat. No. 5,690,692 disclosinga lengthy listing of conditions which may be treated with the aid ofprecise bioactive frequencies. A frequency synthesizer is controlled togenerate a specific precise frequency or a series thereof. A keyboardactuated by a user is employed to select such frequencies, which in turnleads to a circuit which gates the generated signal ON or OFF withindetermined well defined time intervals. Once again, however, influenceson Hdp values or determinations thereof are not considered.

Diagnosis in terms of the present invention may be performed with theaid of certain measured and recorded Hdp parameter values measured, in anumber of patients pre-diagnosed to be suffering from an identified poorhealth condition or being in a healthy condition, at determined timesand for determined periods, as described in greater detail below.

SUMMARY OF THE INVENTION

A hemodynamic parameter (Hdp) monitoring system for diagnosing a healthcondition of a patient, for establishing Hdp marker values or Hdpsurrogate marker values for purposes of comparison with Hdp values of apatient is provided. An Hdp monitor senses, measures, and records Hdpvalues exhibited by the patient during a basal or non-exposure periodand furthermore Hdp values exhibited by the patient during or after anexposure period during which the patient is exposed to low-energyelectromagnetic output signals. An electrically-powered generator isadapted to be actuated to generate said low-energy electromagneticcarrier output signals for exposing or applying to the patient suchoutput signals during said exposure period.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows a block diagram of exemplary circuitry, exemplary ofcircuitry which may be employed as the variable Hdp variation means forapplication of electromagnetic output signals to a patient in accordancewith the present invention.

FIG. 2 shows an example patient during experimental setup for continuousmonitoring of hemodynamic parameters before and during AM RF EMFexposure in accordance with the present invention.

FIG. 3 is an example is eleven hemodynamic parameters simultaneouslymeasured during each heartbeat:

FIG. 4 is a flow diagram representing a hemodynamic recording performedcontinuously during non-exposure and exposure periods in a double-blindfashion.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention provides hemodynamic parameter (Hdp) monitoringsystem for diagnosing a health condition of a patient The systemcomprises a hemodynamic parameter Hdp monitor that senses and recordsvarious identified sensed Hdp values of the patient The system generallysenses various identified sensed Hdp values of the patient utilizingelectrodes placed in topical contact with various determined parts ofthe body. The hemodynamic parameter Hdp monitor further comprisesrecording means that records the various identified sensed Hdp values ofthe patient The recording means can utilize any storage device on whichthe various identified sensed Hdp values of the patient can be recorded.For purposes of diagnosing a health condition of a patient it has beendetermined for purposes of diagnoses performed in accordance with theinvention, that a variety of Hdp values need to be sensed, measured andrecorded, which include the values of at least the following nine Hdp's:

-   -   RR interval (interval from the R peak to the next as shown on an        electrocardiogram (ECG) (RRI);    -   heart rate (HR);    -   systolic blood pressure (sBP);    -   diastolic blood pressure (dBP);    -   median blood pressure (mBP);    -   pulse pressure (PP);    -   stroke volume (SV);    -   cardiac output (CO); and    -   total peripheral resistance (TPR).

The above initial measurements or values thereof are herein named basalmeasurements or basal Hdp values. In terms of procedure, initialmeasurements of above parameters are performed on pre-diagnosed subjectsafter a period of relaxation, for example about 15 minutes, while thepatient is lying in a supine position (face and preferably also palms ofthe hands facing upwardly).

Following on having performed the above initial measurements, thepre-diagnosed subjects are exposed to or application of anHdp-influencing procedure involving exposure to or application ofselected electromagnetic fields (EMF) output signals. The selection ofsuch output signals would generally be based on output signalspredetermined to provide beneficial therapeutic effects in multiplesubjects or rather patients pre-diagnosed to be possessed of anidentified poor health condition.

The above-mentioned EMF output signals may be provided by a generatordevice adapted to generate EMF output signals at certain predeterminedamplitude modulation (AM) frequencies. The subjects or patients are mostpreferably exposed to or the output signals are applied to patientsduring heart-beat times over a determined period of time, mostpreferably over the time of at least ten heart-beat times of thepatient. This procedure would in general take place while the patientremains connected to or is reconnected to the Hdp monitor of the systemof the invention so that Hdp values may be sensed and measured duringthe period of exposure or application. The Hdp values may, however, alsoor alternatively be sensed and measured after the period of exposures orapplications, for purposes of determining potentially lasting effects,generally statistically significant therapeutically beneficial effects,of the exposures or applications to the patient.

The above Hdp values measured during or after above exposures orapplications to pre-diagnosed subjects or patients are herein referredto as post-exposure or Hdp variation values.

The procedures above, in general as applied to multiple patientspre-diagnosed to be suffering from an identified form of poor healthcondition, provide both multiple basal Hdp values and multiplepost-exposure Hdp values as related to the identified pre-diagnosed formof poor health condition. These multiple Hdp values, for example formost if not all of the nine Hdp parameters listed above, may in generalbe somewhat scattered values. Accordingly, for purposes of definingrepresentative marker Hdp values, such scattered values would regularlybe analyzed by statistical procedures for purposes of obtainingrepresentative Hdp values for each of the Hdp parameters.

Conventional statistical procedures might for example include Dixon's Qtest employed for identifying and rejecting outlier values; a T-test fordetermining whether or not mean values of two groups of values arestatistically different from one another; Fisher's discriminantanalysis, standard deviation measures and variance values; and principlecomponent analysis (PCA), a statistical procedure that uses anorthogonal transformation to convert a set of observations of possiblycorrelated variables into a set of values of linearly uncorrelatedvariables called principal components. Values reported herein for Hdpvalues for various Hdp's employ a PCA of correlated variables tolinearly uncorrelated variables (PC's). Hdp values analyzed by suchstatistical procedures serve as markers for so-called surrogate markersemployed for diagnosis of a health condition of a subject [includingvalues for a healthy condition). The surrogates in the present inventionproviding marker values would include numbers of patients pre-diagnosedto be either healthy or suffering from an identified form of a poorhealth condition, such as an identified form of cancer as mentionedbelow.

In line with above, the Hdp monitoring system of the present invention,provides means for establishing and identifying marker values for use indiagnosis of health conditions of a patient The marker values are termedsurrogate markers in that the marker values are determined by themonitoring system following on treatments and Hdp value measurementsperformed on patients pre-diagnosed to be either healthy or sufferingfrom a known form of poor health condition. An Hdp monitor as describedabove is employed in conjunction with a generator device adapted togenerate EM output signals at certain predetermined amplitude modulation(AM) frequencies determined to influence at least certain of the Hdpvalues of the Hdp's listed above. The Hdp monitoring system of theinvention should accordingly include means for sensing and measuring andrecording both basal Hdp values and post-exposure Hdp values ofpatients.

The monitoring system of the invention may furthermore comprise storedinformation including surrogate markers as described above andcomparison means for comparing representative measured Hdp values withrepresentative surrogate markers as described below to provide theindicated diagnosis of a patient undergoing diagnosis. Alternately, thegenerator device may be adapted to receive sensed basal andpost-exposure Hdp values from the Hdp monitor and comprise such storedinformation, which may, if desired, be communicated to the Hdp monitorto provide the attending medical staff with information concerning theindicated diagnosis.

Representative surrogate markers employed for diagnosis purposes, interms of the present invention, are derived from computativecombinations of information from both representative basal Hdp measuredvalues and representative post-exposure or Hdp variance measured values.Since the predetermined AM frequencies employed for influencing Hdpvalues are different for each health condition and post exposure Hdpvalues are similarly different, the computative combinations forderiving representative surrogate markers for a specified healthcondition requires different computations, for example for purposes ofaligning different forms of cancer in a PCA dual group analysis.

The reliability of marker values is of course dependent on the number ofpre-diagnosed surrogates included for each type of poor health conditionexamined. Thus, the incidence of poor health conditions amongpopulations, more particularly high incidence poor health conditionsthat are difficult to diagnose, such as Hepatocellular Carcinoma (HCC)or related liver diseases, has received particular attention. Similarly,the relatively high incidence of breast cancer has thus far alsoreceived particular attention, as reported below.

Post-exposure or Hdp variance measured values, insofar as may bereflected following on exposure to or application of low energy AMcarrier signals, in terms of the invention, may be compared with Hdpvalues which occur following on exposure or application to a patient ofpredetermined AM frequency values pre-determined to alleviate a cause ofa specified poor health condition of a patient. Matching basal andpost-exposure Hdp values, on their own, may both support the efficacy oftreatment by application of said predetermined AM frequency values andprovide a preliminary indication of diagnosis of the health condition ofthe patient Reference to the further scientific details related, forexample, specifically to two different forms of cancer diagnosesdescribed below. Here, mention is made to patient's diagnosis followingon the basal non-exposure period and correlations of patient's diagnosiswith hemodynamic patterns in five (83.3%) of six cases of male HCC, 5(83.3%) of six cases of female breast cancer and six (100.0%) of sixhealthy controls (Table 4). Similarly, mention is made to tumor-specifichemodynamic response pattern during exposure periods (Table 5)

The electrically powered generator of AM electromagnetic output signalsat certain AM frequencies may comprise a storage device for storingpredetermined AM frequency values. Such storage device may be employedfor controlling the AM frequencies of the output signals, as describedin above-mentioned EP Application No. 08 734 777.9-1652.

Alternative to or in addition to comprising a storage device as above,the exposure or application of means for inducing Hdp value variancesmay comprise a variable AM frequency tuning device adapted to vary theAM frequencies between low and high limit values.

The time periods of exposure or application of AM frequency outputsignals by means of a variable frequency tuning device within a broadrange of frequencies; for example, AM frequencies within a range betweenfrom about 0.01 to about 150 MHz, may require a short period of time forHdp values to be varied at any particular frequency value Thus,consecutive exposures or applications of sections of the range of AMfrequencies may be required in order to identify AM frequency values atwhich post-application Hdp value variations actually occur during theheart-beat times at which Hdp values are sensed, measured and recordedby the Hdp monitor.

The system of the invention includes output signal frequency measurementand recording means for measuring and recording such frequency values atwhich frequencies Hdp variances of at least certain of the hemodynamicparameter values are exhibited. Similarly, Hdp value recording means forrecording each of the measured values for each of the identified Hdp's,preferably separately of one another, measured and recorded before,during or after the period of time of exposure to or application ofoutput signals to the patient

A further component of the hemodynamic parameter monitoring system ofthe invention, additional to those described above, is an analyzercomponent which may be integrated with or coupled to the recording meansfor recording hemodynamic parameter values before, during or afterperforming or exposing the patient to a cellular excitation procedure.The analyzer component may include program-controlled calculation meansfor performing statistical analyses of various of the recordedhemodynamic parameter values to obtain representative values for each ofthe different recorded hemodynamic parameter values, optionally making adetermination of ratios between different representative hemodynamicparameter values, and comparing either or both of such representativevalues or ratios between different values, with predeterminedrepresentative values or ratios, predetermined in patients known to behealthy or to be suffering from or likely to develop an identified poorhealth condition. The comparison of calculated representative values forrecorded hemodynamic parameter values or ratios, more particularlyso-called post-excitation hemodynamic parameter variation values, whichmatch with predetermined representative hemodynamic parameter values orratios, leads to providing an indication of a diagnosis of a healthcondition of a patient.

An analyzer component may, alternative or additional to being integratedor coupled to the recording means as described above, be located at ananalysis center which may perform the analyses based on recordedhemodynamic parameter information received or communicated to thecenter.

Example 1

Exemplary of the nine different Hdp values recorded during 16consecutive heart beats are set forth below:

TABLE 1 Hemodynamic Parameter Values Recorded Beat RRI HR sBP dBP mBP PPSV CO TPR 934 976.042 61.473 112.322 63.725 84.556 48.597 57.392 3.5281849.328 935 993.375 60.4 112.716 63.789 85.876 48.927 52.571 3.1752087.994 936 1010.667 59.367 113.369 61.4 85.035 51.969 59.248 3.5171865.839 937 633.042 94.78 110.847 70.266 82.042 40.581 58.303 5.5261144.283 938 1249.708 48.011 111.515 57.736 82.341 53.779 61.038 2.9312165.934 939 990.417 60.581 112.166 61.945 82.065 50.221 64.365 3.8991622.152 940 992.375 60.461 111.238 59.975 82.671 51.263 63.389 3.8331663.034 941 937 64.034 108.904 60.49 79.804 48.414 63.431 4.062 1512.71942 953 62.959 107377 62.11 80933 45.267 64.352 4.052 1538.824 943974.667 61.56 111.219 62.063 83.48 49.156 67.078 4.129 1559.211 944696.375 86.16 110.614 67.459 84.906 43.155 65.59 5.651 1159.47 9451214.333 49.41 110.84 57.562 81.261 53.278 65.046 3.214 1948.051 946985.75 60.867 109.052 62.014 79.855 47.038 66.379 4.04 1521.775 9471002.667 59.84 111.222 61.649 83.616 49.573 65.568 3.924 1643.7 948600.875 99.854 111.588 70.895 83.465 40.693 66.216 6.612 973.56 9491281.5 46.82 107.484 54.898 78.606 52.586 59.847 2.802 2158.584 9501017.333 58.978 107.438 60.796 78.035 46.642 61.743 3.641 1648.453

The above sensed and recorded values for each of the nine hemodynamicparameters are exemplary of such values exhibited by a single patient.

Example 2

The following Table 2 is exemplary Principal Component [PC) values,representative of a multiple number of sensed and recorded hemodynamicparameter values for each of the nine values of a number of patients.The PC representative values are divided into three groups: Pressure,Flow and Beat for three groups each of 8 patients, respectively 8patients with hepatocellular carcinoma (HCC), 8 patients with breastcancer, and 8 healthy controls for simplifying comparisons of PC Hdpvalues between patients with a diagnosis of HCC or breast cancer andhealthy controls. Also included in the following Table is reference to Xand Y canonical coordinates obtained by the Fisher's discriminantanalysis, representative pressure, flow and beat PC values of Hdp'sexhibited by patients before exposures or applications of EM AM signals:

TABLE 2 Diagnosis based on Hemodynamic parameter (Hdp) lineardiscriminate and PC Analyses HCC Coordinate Coordinate Pressureprincipal components Flow principal components Beat principal componentsPatient Code X Y PI P2 P3 F1 F2 F3 B1 B2 B3 55 −0.405 −0.032 0.932−0.056 0.016 0.205 0.376 0.081 −0.01 −0.011 0.001 56 −0.39 −0.024 0.888−0.041 0.094 0.124 0.337 0.012 0.002 0.004 −0.001 59 −0.418 −0.021 0.8990.066 0.069 0.214 0.125 0.291 −0.003 0.002 −0.012 60 −0.411 −0.02 0.8340.058 0.031 0.249 0.326 −0.007 −0.002 −0.002 −0.001 62 −0.377 −0.0170.87 0.044 0.139 0.211 0.309 −0.029 −0.009 −0.002 0.003 77 −0.388 −0.0060.781 −0.115 0.036 0.119 0.344 0.019 −0.002 −0.002 0 78 −0.39 −0.0150.869 −0.075 −0.006 0.194 0.385 0.141 0.004 0.002 0 82 −0.348 −0.0250.986 0.099 0.09 0.391 0.091 0.611 0.001 0 0 Breast cancer X Y P1 P2 P3F1 F2 F3 B1 B2 B3 39 0.327 −0.033 0.804 −0.007 0.044 0.172 0.337 0.044−0.001 −0.001 0 41 0.327 −0.034 0.838 −0.038 0.091 0.239 0.369 −0.0020.001 0.002 0.001 42 0.316 −0.014 0.116 0.067 0.752 0.027 0.318 0.116 00.002 −0.001 45 0.296 −0.033 0.853 0.103 0.054 0.266 0.088 0.318 −0.0080.002 0.004 46 0.292 −0.024 0.683 0.057 −0.049 0.127 0.001 0.323 −0.003−0.018 −0.023 47 0.285 −0.021 0.838 0.062 −0.221 0.193 0.034 0.324 0.015−0.014 0.059 48 0.299 −0.025 0.862 0.086 −0.134 0.169 0.046 0.349 0.0010 0 49 0.324 −0.032 0.849 −0.069 0.066 0.225 0.378 0.047 0 −0.002 0.001Healthy Individuals X Y P1 P2 P3 F1 F2 F3 B1 32 B3 4 −0.275 0.002 0.2310.815 −0.01 0.054 0.099 0.337 −0.001 0.006 −0.003 7 −0.284 0.037 0.8520.257 −0.089 0.154 0.148 0.342 0.009 0 0 12 −0255 0.043 0.351 0.2110.507 0.278 −0.256 0.126 −0.003 −0.008 −0.001 13 −0.32 0.052 0.917 0.0050.024 0.251 0.382 0.062 0.003 0.001 0 17 −0.591 0.015 0.731 −0.095 0.140.094 0.352 −0.029 −0.001 −0.002 −0.001 23 −0.572 0.014 0.872 0.195−0.035 0.213 0.234 0.374 −0.009 0.003 −0.015 75 −0.341 0.003 0.193 0.807−0.222 0.197 0.141 0.287 0.002 0.07 0.027 79 −0.344 0.007 0.256 0.72−0.014 −0.042 0.151 0.346 −0.002 0.019 0.003

Of interest from the above figures is firstly that all patients with adiagnosis of cancer, in this example both patients with diagnosis of HCCand patients with diagnosis of breast cancer reflect PI PC values whichare significantly greater than the P2 PC values.

Example 3

The following Table 3 is exemplary discrimination by analytical geometryusing canonical coordinates and vectors obtained from PC values,representative of a multiple number of sensed and recorded hemodynamicparameter values for each of the nine values of a number of patients.The PC representative values are divided into three groups, Pressure,Flow and Beat for three groups each of the patients, respectively withHCC, patients with breast cancer, and healthy controls. For determiningthe generalized squared distance to d group of values using lineardiscriminant function of geometric parameters, the distinct group ofpatients based on their diagnosis is identified:

TABLE 3 Diagnosis based on hemodynamic parameter (Hdp), lineardiscriminant and geometry analyses d_group Cancer Healthy Cancer 0120.49729 Healthy 120.49729 0 LDA constant −0.89418 −68.98654 area oftriangle 0.0171 0.33941 Apotema P-B −0.15385 −3.18876 Apotema B-F0.40858 2.7007 Apotema F-P −0.00324 0.65841 Area of circle −0.001−0.0002036 D_group HCC Breast Healthy HCC 0 0.96372 119.23965 Breast0.96372 0 118.8079 Healthy 119.23965 118.8079 0 LDA constant −1.56828−0.58072 −68.04536 Area of triangle 0.0159 0.01733 0.33439 Apotema P-B−0.07174 −0.19523 −3.12901 Apotema B-F 0.4447 0.37987 2.666957 ApotemaF-P 0.03225 −0.02252 0.6553 Area of circle −0.00176 −0.0005698−0.0003422

Referring to FIG. 1, a block diagram of exemplary circuitry, exemplaryof circuitry which may be employed as the variable Hdp variation meansfor application of electromagnetic output signals to a patient is seen.Such exemplary circuitry may be provided with connection means forconnection to or may be comprised or integrated into in the hemodynamicparameter monitoring system of the invention. Descriptions of each ofthe blocks of the block diagram or functions thereof are included tofacilitate an understanding thereof.

The block diagram of electronic circuitry of an application systemapplies AM RF output signals to a patient at predetermined selected AMfrequencies. The predetermined selected frequencies are controlled by AMfrequency values stored in storage device 52. The stored predeterminedAM frequency values are separately determined by biofeedback proceduresperformed on patients and stored in storage device 52. Variouspredetermined selected AM frequencies applied to a patient are indicatedfor treatment of patients suffering from one or other form of a poorhealth condition of a patient.

Extended clinical trials performed with the aid of above applicationsystem led to a discovery that cancerous cell growth or proliferationthereof in patients may be inhibited by application to patients of AMoutput signals at certain well-defined frequencies. Furtherinvestigations revealed that the AM frequencies for purposes of cancertreatment need to be very accurately controlled. Patent Applicationsfiled on a world-wide basis, such as represented by EP 08 734 777.9 orPCT EP 2008 002 379, International Publication WO 2008 116 640 A2,related to this discovery and investigations, including the identity ofvery accurate AM frequency values of output signals for identified formsof cancer and a modified system enabling application to a patient ofsuch very accurately controlled AM frequency output signals. Themodification to the system comprised in EP 08 734 777.9 includes aso-called Digital Direct Synthesizer (DDS) which may be combined withthe illustrated microprocessor 21.

The present invention contemplates employing a device or modified deviceas described above or indeed other devices described in the art, such asdescribed U.S. Pat. No. 5,690,692 assigned to Regeneration Technology ofTijuana, Mexico, in combination with a hemodynamic parameter monitoringsystem able to sense and measure at least the nine hemodynamic parametervalues referred to above. More particularly, such a combination enablessensing of hemodynamic parameter values of a patient both prior to,during or after application to the patient of AM RF electromagneticsignals as described in prior literature or other such signals as may beapplied to the patient. Of particular interest in this regard is thatsensed, measured and recorded hemodynamic parameter (Hdp) values differdependently of the patient condition. For example, as exemplified above,sensed and recorded hemodynamic parameter values differ between patientssuffering from different forms of cancer and differ from such values ofhealthy patient conditions. Moreover, it appears that such hemodynamicparameter values are shared, at least to a major extent, by patientssuffering from the same or a closely related poor health condition. Thesensed and recorded hemodynamic parameter values accordingly offerdiagnosis opportunities for diagnosing various forms of poor healthconditions of a nature such as mentioned above and also diagnosis ofhealthy patient conditions.

Additional to the combination of the invention as discussed above,modifications to the treatment devices or systems described in prior artdisclosures are contemplated in terms of the present invention. Moreparticularly, following on determinations of sensed and recorded Hdpvalues made in a large variety of patients which have been treated withthe aid of earlier systems, it is considered that the requirements forgenerating specific precise frequencies or a series of preciseprogrammed frequencies may be replaced or supplemented by a variablefrequency tuning device, variable between lower and upper frequencylimits, which is activated during a time that a patient is connected toa hemodynamic parameter monitor of the nature described.

The availability of such a variable frequency tuning device, incombination with the hemodynamic parameter monitor, would enable sensingof Hdp values required in terms of the invention at various frequencyvalues. The frequency values may be selected from frequency valuessuggested in terms of prior disclosures for determining the effects onHdp values or variations thereof. However, such frequency values atwhich Hdp values or variations thereof which are of interest may berecorded. Recorded frequency values may be compared to predeterminedfrequency values proposed in earlier disclosures for treatment ofpatients in support of the identity or accuracy thereof or may provideinformation related to additional frequency values which may providebeneficial therapeutic effects on patients suffering from a poor healthcondition.

Availability of a variable frequency tuning device, available forvarying the frequency of low energy AM output signals during the time ofexposure or application of Hdp variation means to a patient is amodification considered may be of practical importance. Thus, incontrast to treatment devices disclosed in prior literature, thefrequencies employed for various treatments of patients are invariablypredetermined stored frequencies. In this regard, above-mentioned U.S.Pat. No. 5,690,692 might be considered to suggest availability of afrequency tuning device following on disclosure of “ . . . the frequencysignal is gradually increased at a predetermined rate from zero to apredetermined level controllable by a user.” In fact, what is here beingreferred to is gradual increase of variable amplitudes of signals andnot frequencies of amplitude modulations or simply the frequency thatthe described square wave output signals occur. As in other priorliterature, U.S. Pat. No. 5,690,692 relies on predetermined frequencyvalues for performing treatment procedures.

Referring back to FIG. 1, microprocessor 21 operates as the controllerfor the application system and is connected to control the variouscomponents of the system through address bus 22, data bus 23 andinput/output (I/O) lines 25. Microprocessor 21 preferably includesinternal storage for the operation code, control program, and temporarydata. In addition, microprocessor 21 includes input/output (I/O) portsand internal timers. Microprocessor 21 may, for example, be an 8-bitsingle-chip micro-controller, 8048 or 8051 available from IntelCorporation, 2200 Mission College Boulevard, Santa Clara, Calif. 95054U.S. The timing for microprocessor 21 is provided by system clock 24which includes a clock crystal 26 along with capacitors 27 and 28.System clock 24 may run at any clock frequency suitable for theparticular type of microprocessor used. In accordance with oneembodiment, system clock 24 operates at a clock frequency of 8.0 MHz.

In general, microprocessor 21 functions to control controllableelectromagnetic energy generator circuit 29 to produce a desired form ofmodulated low energy electromagnetic emission for application to apatient through probe 13. Controllable generator circuit 29 includesmodulation frequency generator circuit 31 and carrier signal oscillator32. Microprocessor 21 operates to activate or de-activate controllablegenerator circuit 29 through oscillator disable line 33. Controllablegenerator circuit 29 also includes an AM modulator and power generator34 which operates to amplitude modulate a carrier signal produced bycarrier oscillator 32 on carrier signal line 36, with a modulationsignal produced by modulation signal generator circuit 31 on modulationsignal line 37. Modulator 34 produces an amplitude modulated carriersignal on modulated carrier signal line 38, which is then applied to thefilter circuit 39. The filter circuit 39 is connected to probe 13 viacoaxial cable 12 and impedance transformer 14.

Microprocessor 21 controls modulation signal generator circuit 31 ofcontrollable generator circuit 29 through address bus 22, data bus 23and I/O lines 25. In particular, microprocessor 21 selects the desiredwaveform stored in modulation waveform storage device 43 via I/O lines25. Microprocessor 21 also controls waveform address generator 41 toproduce on waveform address bus 42 a sequence of addresses which areapplied to modulation signal storage device 43 in order to retrieve theselected modulation signal. The desired modulation signal is retrievedfrom wave form look-up table 43 and applied to modulation signal bus 44in digital form. Modulation signal bus 44 is applied to digital toanalog converter (DAC) 46 which converts the digital modulation signalinto analog form. This analog modulation signal is then applied toselective filter 47 which, under control of microprocessor 21, filtersthe analog modulation signal by use of a variable filter networkincluding resistor 48 and capacitors 49 and 51 in order to smooth thewave form produced by DAC 46 on modulation signal line 20.

In the present embodiment, the various modulation signal wave forms arestored in look-up table 43. With a 2 kilobyte memory, look-up table 43may contain up to 8 different modulation signal wave forms. Wave formswhich have been successfully employed include square wave forms orsinusoidal wave forms. Other possible modulation signal wave formsinclude rectified sinusoidal, triangular, and combinations of all of theabove.

In the present embodiment, each modulation signal wave form uses 256bytes of memory and is retrieved from look-up table 43 by runningthrough the 256 consecutive addresses. The frequency of the modulationsignal is controlled by how fast the wave form is retrieved from look-uptable 43. In accordance with the present embodiment, this isaccomplished by downloading a control code from microprocessor 21 intoprogrammable counters contained within wave form address generator 41.The output of the programmable counters then drive a ripple counter thatgenerates the sequence of 8-bit addresses on the wave form address bus42.

Wave form address generator 41 may, for example, be a programmabletimer/counter uPD65042C, available from NEC. Modulation signal storagedevice or look-up table 43 may, for example, be a type 28C16 ElectricalErasable Programmable Read Only Memory (EEPROM) programmed with thedesired wave form table. Digital to analog converter 46 may, forexample, be a DAC port, AD557JN available from Analog Devices, andselective filter 47 may be a type 4052 multiplexer, available fromNational Semiconductor or Harris Semiconductor.

The particular modulation control information used by microprocessor 21to control the operation of controllable generator circuit 29, inaccordance with the present invention, is stored in application storagedevice 52 or, in terms of the present invention may be a variable AMfrequency tuning device adapted to load the interface 16 with AMfrequencies between and high and low frequency levels. Applicationstorage device 52 may be any storage device capable of storinginformation for later retrieval. For example, application storage device52 may be, for example, a magnetic media based storage device such as acard, tape, disk, or drum. Alternatively, application storage device 52may be a semiconductor memory-based storage device such as an erasableprogrammable read only memory (EPROM), an electrical erasableprogrammable read only memory (EEPROM) or a non-volatile random accessmemory (RAM). Another alternative for application storage device 52 is amechanical information storage device such as a punched card, cam, orthe like. Yet another alternative for application storage device 52 isan optical storage device such as a compact disk read only memory (CDROM).

It should be emphasized that although the figures illustratemicroprocessor 21 separate from application storage device 52,microprocessor 21 and application storage device 52 may both beincorporated into a single device, which is loaded into the system tocontrol the operation of the system as described herein. In this case,interface 16 would exist between the combination of microprocessor 21and application storage device 52 and the rest of the system.

Interface 16 is configured as appropriate for the particular applicationstorage device 52 in use. Interface 16 translates the controlinformation stored in application storage device 52 into a usable formfor storage within the memory of microprocessor 21 to enablemicroprocessor 21 to control controllable generator circuit 29 toproduce the desired modulated low energy emission. Interface 16 maydirectly read the information stored on application storage device 52,or it may read the information through use of various knowncommunications links. For example, radio frequency, microwave, telephoneor optical based communications links may be used to transferinformation between interface 16 and application storage device 52. Whenapplication storage device 52 and microprocessor 21 are incorporated inthe same device, interface 16 is configured to connect microprocessor 21to the rest of system.

The control information stored in application storage device 52specifies various controllable parameters of the modulated low energy RFelectromagnetic emission which is applied to a patient through probe 13.Such controllable parameters include, for example, the frequency andamplitude of the carrier, the amplitudes and frequencies of themodulation of the carrier, the duration of the emission, the power levelof the emission, the duty cycle of the emission (i.e., the ratio of ontime to off time of pulsed emissions applied during an application), thesequence of application of different modulation frequencies for aparticular application, and the total number of treatments and durationof each treatment prescribed for a particular patient.

For example, the carrier signal and modulation signal may be selected todrive the probe 13 with an amplitude modulated signal in which thecarrier signal includes spectral frequency components below 1 GHz, andpreferably between 1 MHz and 900 MHz, and in which the modulation signalcomprises spectral frequency components between 0.1 Hz and 10 KHz, andpreferably between 1 Hz and 150 KHz. In accordance with the presentinvention, one or more modulation frequencies may be sequenced to formthe modulation signal.

As an additional feature, an electromagnetic emission sensor 53 may beprovided to detect the presence of electromagnetic emissions at thefrequency of the carrier oscillator 32. Emission sensor 53 provides tomicroprocessor 21 an indication of whether or not electromagneticemissions at the desired frequency are present. Microprocessor 21 thentakes appropriate action, for example, displaying an error message oninformation output display 17, disabling controllable generator circuit29, or the like.

The invention also includes a power sensor 54 which detects the amountof power applied to the patient through probe 13 compared to the amountof power returned or reflected from the patient. This ratio isindicative of the proper use of the system during a therapeutic session.Power sensor 54 applies to microprocessor 21 through power sense line 56an indication of the amount of power applied to patient through probe 13relative to the amount of power reflected from the patient.

The indication provided on power sense line 56 may be digitized and usedby microprocessor 21, for example, to detect and control a level ofapplied power, and to record on application storage device 52,information related to the actual treatments applied. Such informationmay then be used by a physician or other clinician to assess patienttreatment compliance and effect. Such treatment information may include,for example: the number of treatments applied for a given time period;the actual time and date of each treatment; the number of attemptedtreatments; the treatment compliance (i.e., whether the probe was inplace or not in place during the treatment session); and the cumulativedose of a particular modulation frequency.

The level of power applied is preferably controlled to cause thespecific absorption rate (SAR) of energy absorbed by the patient to befrom 1 microwatt per kilogram of tissue to 50 Watts per kilogram oftissue. Preferably, the power level is controlled to cause an SAR offrom 100 microwatts per kilogram of tissue to 10 Watts per kilogram oftissue. Most preferably, the power level is controlled to deliver wholebody mean SAR in the range of only 0.2 to 1 mW/kg, with a 1 g peakspatial SAR between 150 and 350 mW/kg These SARs may be in any tissue ofthe patient. The system also includes powering circuitry includingbattery and charger circuit 57 and battery voltage change detector 58.

In that an association, combination or use of a device of the naturedescribed above in conjunction with a hemodynamic parameter monitoringdevice enabling sensing, measuring and recording the at least nineparameter values mentioned, before, during or after exposure orapplication of Hdp influencing means has provided for previously unknownmethods of diagnosing health conditions of a patient, further scientificdetails related, for example, specifically to two different forms ofcancer diagnoses are provided below:

INTRODUCTION

The identification of changes in pulse amplitude in patients with adiagnosis of cancer when exposed to low and safe levels of 27.12 MHzradiofrequency electromagnetic fields amplitude-modulated at specificfrequencies have previously been reported. (Barbault, A. et al.Amplitude-modulated electromagnetic fields for the treatment of cancer:discovery of tumor-specific frequencies and assessment of a noveltherapeutic approach. J. Exp. Clin. Cancer Res. 28, 51,doi:10.1186/1756-9966-28-51 (2009)). The observation that changes inpulse amplitude occur at exactly the same frequencies in patients withthe same type of cancer led to a hypothesis that each type of cancerpossesses a specific frequency signature. (Yd.) In vitro experimentshave shown that tumor-specific frequencies have anti-proliferativeeffects on cancer cells, modulate the expression of genes involved incell migration and invasion, and are capable of disrupting the mitoticspindle. (Zimmerman, J. W. et al. Cancer cell proliferation is inhibitedby specific modulation frequencies. British Journal of Cancer 106,307-313 (2012)). The clinical activity of these tumor-specificfrequencies was assessed in two separate studies in which patients weretreated with intrabuccally administered AM RF EMF, which were modulatedat tumor-specific frequencies. Antitumor activity was observed inpatients with metastatic breast cancer (Barbault, A. et al. (2009)) andadvanced hepatocellular carcinoma (Costa, F. P. et al. Treatment ofadvanced hepatocellular carcinoma with very low levels ofamplitude-modulated electromagnetic fields. British Journal of Cancer105, 640-648 (2011)) and stable disease was observed in patients withother tumor types.

This study was designed to test the hypothesis that analysis of changesin hemodynamic parameters upon exposure to tumor-specific frequencies isa novel, non-invasive cancer diagnostic approach.

MATERIALS AND METHODS

The experimental procedures described below were reviewed and approvedby the Hospital Sfrio Libanês Institutional Review Board (IRB), Rua DonaAdma Jafet, 50 Conj.41/43, Sao Paulo SP 01.308-050 Brazil. All patientsand healthy individuals enrolled in this study signed an informedconsent, which was approved by the IRB. The protocol was registeredprior to enrolment of the 1st patient: clinicaltrial.gov identified no.NCT 01686412. 87 individuals were screened and 82 individuals wereprospectively enrolled. The discovery group consisted of eight patientswith a diagnosis of advanced HCC, six patients with a diagnosis ofadvanced breast cancer, and six healthy controls. The patient'sdiagnosis and the nature of AM RF EMF exposure (HCC-specific, breastcancer specific, and randomly chosen frequencies) were disclosed beforecomputational analysis. The validation group consisted of 25 patientswith biopsy-proven cancer (11 with advanced HCC and 14 with advancedbreast cancer), and 31 healthy controls. The last group consisted of sixpatients with potentially resectable HCC

Three separate groups of patients and healthy controls were analyzed inthis study: 1) The discovery group consisted of eight patients withadvanced hepatocellular carcinoma, six patients with advanced breastcancer, and six healthy controls; 2) The validation group consisted of25 patients with a diagnosis of cancer (14 female patients with advancedbreast cancer and 11 male patients with advanced HCC) and 31 healthycontrols (18 females and 13 males); and 3) six patients (five males andone female) with potentially resectable hepatocellular carcinoma.

Intrabuccal Administration of AM RF EMF:

The AM RF EMF device used for this study has been described in detailpreviously. (Costa, F. P. et al. British journal of cancer 105, 640-648(2011)). While patients receiving treatment with AM RF EMF are exposedto three daily one hour treatments, the diagnostic feasibility of AM RFEMF administration was tested during a single 10 minute exposure inorder to expose all individuals once to each of the 194 tumor-specificfrequencies (HCC specific and breast cancer specific), which are eachemitted for three seconds. (Barbault, A. et al. J. Exp. Clin. CancerRes. 28, 51, doi:10.1186/1756-9966-28-51 (2009); Zimmerman, J. W. et al.British Journal of Cancer 106, 307-313 (2012); Costa, F. P. et al.British Journal of Cancer 105,640-648 (2011)). Similarly, 194 of thepreviously reported 236 randomly chosen frequencies were selected(Zimmerman, J. W. et al. British Journal of Cancer 106, 307-313 (2012)to match the number and exposure duration of tumor-specific frequencies.Hence, each individual was exposed to all frequencies included in eachof the treatment programs (HCC specific, breast cancer specific, andrandomly chosen frequencies), i.e. each modulation frequency emitted forthree seconds from the lowest to the highest frequency as previouslydescribed. ((Barbault, A. et al. J. Exp. Clin. Cancer Res. 28, 51,doi:10.1186/1756-9966-28-51 (2009); Zimmerman, J. W. et al. Britishjournal of cancer 106, 307-313 (2012); Costa, F. P. et al. Britishjournal of cancer 105, 640-648 (2011)).

Hemodynamic Parameter Monitoring:

Referring to FIG. 2, an example patient is seen during experimentalsetup for continuous monitoring of hemodynamic parameters before andduring AM RF EMF exposure. Non-invasive hemodynamic measurement wasperformed using a Task Force® Monitor (CNSystems Medizintechnik GmbH,version 2.2.12.0, Reininghausstraβe 13, 8020 Graz, Austria). Numericalvalues of heart rate, blood pressure and blood flow are measured bydigital photoplethysmography, pressure cuff and ECG. The hemodynamicparameters are transformed into absolute values for each consecutiveheartbeat before and during AM RF EMF exposure. The spoon-shaped antennafor intrabuccal administration of AM RF EMF was placed in the patient'smouth during the entire experiment. In FIG. 2, the Task Force® monitoris labelled 1. The AM RF EMF emitting device is labelled 2. The AM RFEMF emitting device connected to a coaxial cable, which is connected tothe spoon-shaped antenna 3. A right arm digital pressure cuff islabelled 4. A digital photoplethysmography is labelled 5. A left armdigital pressure cuff is labelled; 6. Electrodes' cables for ECG andimpedance cardiography are provided.

Numerical values of heart rate variability, blood pressure, baroreceptorsensitivity and blood pressure were measured by digitalphotoplethysmography and ECG acquired through three thoracic adhesiveelectrodes for high resolution for RR interval analysis. Digitalpressure cuff was placed on the right arm and around the middle phalanxof the third and fourth right finger and another on the left arm betweenthe shoulder and the elbow. Blood pressure measurements were transformedinto absolute values for each consecutive heartbeat.

Referring to FIG. 3, an example is seen of eleven hemodynamic parameterssimultaneously measured during each heartbeat: heart rate (HR), systolicblood pressure (sBP), median blood pressure (mBP), diastolic bloodpressure (dBP), total peripheral resistance (TPR), total peripheralresistance index (TPRI), cardiac output (CO), cardiac index (CI), RRinterval (RRI), stroke volume (SV), and systolic index (SI). Hemodynamicrecording was performed continuously in supine position before andduring exposure to AM RF EMF. A total of three million hemodynamicparameters were analyzed in this study.

Participants held the spoon-shaped antenna in their mouth during theentire experiment The three different devices each programmed with oneof the treatment programs (HCC specific, breast cancer specific, andrandomly chosen frequencies) were connected prior to initiation of eachof the AM RF EMF exposure period. The protocol was conducted in adouble-blind fashion.

Referring to FIG. 4, hemodynamic recording was performed continuouslyduring non-exposure and exposure periods in a double-blind fashion. Thenon-exposure periods were the initial basal and five minute restingintervals between RF EMF exposures. During the exposure periods,patients received AM RF EMF (HCC-specific, breast cancer-specific,randomly chosen frequencies).

Computational Analysis:

Hemodynamic parameters were analyzed according to three factors:diagnosis (HCC, breast cancer, healthy control), gender, and recordingperiod (baseline and exposure to HCC-specific, breast cancer-specific,and randomly chosen modulation frequencies).

Analysis of the recorded hemodynamic data was only conducted aftercompletion of patient accrual. Data analysis began with the discoverygroup (six healthy controls, six patients with advanced HCC, and sixpatients with advanced breast cancer). The anticipated outcome of thediscovery group analysis was the creation of computative specific forpatients with hepatocellular carcinoma, patients with breast cancer, andhealthy controls. Once the computations were constructed, the data fromthe validation group was analyzed in a blinded fashion in order tovalidate the computative.

Analysis of six patients diagnosed with potentially resectable HCC wasconducted after the completion of the validation group analysis. Thesepatients underwent the same non-invasive hemodynamic parametermeasurements within 24 hour prior to HCC surgical resection and aftercomplete recovery within four to six weeks post-surgery. Pre- vspost-surgical analysis was conducted.

Results Discovery Group Hemodynamic Pattern Identification Based onDiagnosis Analysis of Baseline Measurements:

Analysis of hemodynamic parameters during the basal non-exposure periodwas significantly different among six male healthy controls, sixpatients with hepatocellular carcinoma, and six female patients withbreast cancer in the “Discovery Group” (p<0.0001). Having observedsignificant differences in hemodynamic parameters between male andfemale participants and taking into account the fact that the first sixpatients with HCC were male, two female patients with HCC weretransferred from the validation group to the discovery group prior tothe analysis of the validation group.

Discovery of Patient's Hemodynamic Pattern:

Hemodynamic parameter analysis during the basal non-exposure periodrevealed four different hemodynamic patterns in the discovery group. Thepatient's diagnosis correlated with hemodynamic pattern in 5 (83.3%) ofsix cases of male HCC, 5 (83.3%) of six cases of female breast cancerand six (100.0%) of six healthy controls, seen in Table 4:

TABLE 4 Determination of four distinct hemodynamic patterns and theircorrelation in patients with diagnosis of cancer and without cancer inthe Discovery Group. male female Healthy Breast Healthy Correlation HCCcontrol cancer control with diagnosis (%) (%) (%) (%) Total Correctcorrelation 5 (83.3) 3 (100.0) 5 (83.3) 3 (100.0) 16 Wrong correlation 1(16.7  0 1 (16.7) 0 2 total 6 3 6 3 18

Discovery of Tumor-Specific Hemodynamic Response Pattern During ExposurePeriods:

Each AM RF EMF exposure (HCC-specific, breast cancer-specific, andrandomly chosen modulation frequencies) could be tested independently bythe computative. A similar hemodynamic response pattern in six (100.0%)of six patients with HCC, which only occurred during exposure toHCC-specific modulation frequencies was observed, seen in Table 5:

TABLE 5 Identification of cancer specific hemodynamic response patternupon exposure to AM RF EMF modulated at specific and non-specificfrequencies in patients with diagnosis of cancer in the Discovery GroupHCC Breast cancer Cancer-specific Non-cancer specific Cancer-specificNon-cancer specific Cancer-specific frequencies frequencies frequenciesfrequencies Hemodynamic # exposures # exposures Total # exposures #exposures Total response pattern (%) (%) exposures (%) (%) exposurescancer specific pattern 6 (100.0  0 6 5 (83.3) 1 (14.3) 6 non-cancerpattern 0 12 (100.0) 12 1 (16.7) 11 (91.6)  12 total exposures 6 (100.0)12 (100.0) 18  6 (100.0) 12 (100.0) 18

In patients with breast cancer, application of a computative identifieda similar hemodynamic response pattern in 5 (83.3%) of six cases, whichonly occurred during exposure to breast cancer-specific modulationfrequencies (Table 2). Hence, in patients with a diagnosis of cancer atumor-specific hemodynamic response pattern was correctly identified in11 (91.6%) of 12 exposures to the corresponding tumor-specificmodulation frequencies. A tumor-specific hemodynamic response in onlyone (4%) of 24 exposures to randomly chosen modulation frequencies wasobserved.

Validation Group and Surgical Group Validation of Baseline HemodynamicPattern Computations:

A correct diagnosis based on baseline hemodynamic pattern was made in 9(81.8%) of 11 cases of HCC, 12 (85.7%) of 14 cases of breast cancer and21 (67.7%) out of 31 healthy controls, as seen in Table 6:

TABLE 6 Determination of four distinct hemodynamic patterns and theircorrelation in patients with diagnosis of cancer and without cancer inthe Validation Group male female Healthy Breast Healthy Correlation HCCcontrol cancer control with diagnosis (%) (%) (%) (%) Total Correct 11(100.0) 9 (69.2) 14 (100.0) 17 (94.4) 51 correlation Wrong 0 4 (30.8) 01 (5.6) 5 correlation total 11 (100.0) 13 (100.0) 14 (100.0)  18 (100.0)56 Sensitivity 100.0% 100.0% Specificity 69.2% 94.4%

Validation of tumor-specific hemodynamic response pattern during AM RFEMF exposure: The HCC-specific hemodynamic response pattern wasidentified in 10 (90.0%) of 11 cases of HCC patients (Table 4). Thebreast cancer-specific hemodynamic response pattern was identified in 12(85.7%) of 14 female patients with breast cancer, as seen in Table 7:

TABLE 7 Identification of cancer specific hemodynamic response patternupon exposure to AM RF EMF modulated at specific and non−specificfrequencies in patients with diagnosis of cancer in the Validation GroupHCC Breast cancer Cancer specific Cancer specific Non-cancer specificCancer specific Non-cancer specific Hemodynamic frequencies frequenciesTotal frequencies frequencies Total response pattern # exposures (%) #exposures (%) exposures # exposures (%) # exposures (%) exposures Cancerspecific pattern 6 (100.0) 0 6 5 (83.3) 1 (14.3) 6 Non-cancer pattern 012 (100.0) 12 1 (16.7) 11 (91.6)  12 Total exposures 6 (100.0) 12(100.0) 18  6 (100.0) 12 (100.0) 18

Female HCC analysis: female patients with HCC were found to have thesame hemodynamic pattern and hemodynamic response pattern to AM RF EMFas males with HCC, as seen in Table 8:

TABLE 8 Determination of four distinct hemodynamic patterns and theircorrelation with diagnosis and determination of cancer specifichemodynamic response pattern upon exposure to AM RF EMF modulated atspecific and non-specific frequencies in male and female patientsdiagnosed with HCC Correlation with diagnosis HCC (%) Male Female TotalCorrect correlation 6 (75.0) 5 1 6 Wrong correlation 2 (25.0) 1 1 2total  8 (100.0) 6 2 8 Male Female Cancer-specific Cancer-specificCancer-specific Cancer-specific Hemodynamic frequencies frequenciesfrequencies Total response pattern # exposures (%) # exposures #exposures # exposures cancer specific pattern 8 (100.0) 6 2 8 non-cancerpattern 0 0 0 0 total exposures 8 (100.0) 6 2 8HCC Specific Hemodynamic Response Pattern Before and after SurgicalResection:

There was no significant change in the hemodynamic patterns during thebasal non-exposure period and exposure to randomly chosen and breastcancer-specific modulation frequencies. On the contrary, there was asignificant difference between the pre- and the post-resectionhemodynamic response pattern during exposure to HCC-specific modulatedfrequencies in six (100%) of six patients.

Pre-Specified Post-Hoc Analysis:

Combined analysis of all 74 individuals led to the identification ofrefined hemodynamic pattern criteria. These refined criteria result inbetter hemodynamic pattern characterization between patients with adiagnosis of cancer and healthy controls. Correlation betweenhemodynamic pattern and patient diagnosis was achieved in 16 (100.0%) of16 patient with HCC, 20 (100.0%) of 20 patients with breast cancer and32 (86.4%) of 37 healthy controls.

In accordance with the present invention, the identification andcharacterization of new methods allowing for the diagnosis ofhepatocellular carcinoma and breast cancer in a blinded fashion basedsolely on hemodynamic parameters measured before and during exposure to27.12 MHz RF EMF amplitude modulated at tumor-specific frequencies areprovided. These findings may have broad clinical implications for thediagnosis of cancer.

While the invention has been described with specific embodiments, otheralternatives, modifications, and variations will be apparent to thoseskilled in the art. Accordingly, it will be intended to include all suchalternatives, modifications and variations set forth within the spiritand scope of the appended claims.

TABLE 1 Hemodynamic Parameter Values Recorded Beat RRI HR sBP dBP mBP PPSV CO TPR 934 976.042 61.473 112.322 63.725 84.556 48.597 57.92 3.5281849.328 935 993.375 60.4 112.716 63.789 85.876 48.927 52.571 3.1752087.994 936 1010.667 59.367 113.369 61.4 85.035 51.969 59.248 3.5171865.839 937 633.042 94.78 110.847 70.266 82.042 40.581 58.303 5.5261144.283 938 1249.708 48.011 111.515 57.736 82.341 53.779 61.038 2.9312165.934 939 990.417 60.581 112.166 61.945 82.065 50.221 64.365 3.8991622.152 940 992.375 60.461 111.238 59.975 82.671 51.263 63.389 3.8331663.034 941 937 64.034 108.904 60.49 79.804 48.414 63.431 4.062 1512.71942 953 62.959 107.377 62.11 80.933 45.267 64.352 4.052 1538.824 943974.667 61.56 111.219 62.063 83.48 49.156 67.078 4.129 1559.211 944696.375 86.16 110.614 67.459 84.906 43.155 65.59 5.651 1159.47 9451214.333 49.41 110.84 57.562 81.261 53.278 65.046 3.214 1948.051 946985.75 60.867 109.052 62.014 79.855 47.038 66.379 4.04 1521.775 9471002.667 59.84 111.222 61.649 83.616 49.573 65.568 3.924 1643.7 948600..875 99.854 111.588 70.895 83.465 40.693 66.216 6.612 973.56 9491281.5 46.82 107.484 54.898 78.606 52.586 59.847 2.802 2158.584 9501017.333 58.978 107.438 60.796 78.035 46.642 61.743 3.641 1648.453

TABLE 2 Diagnosis based on Hemodynamic parameter (Hdp) lineardiscriminate and PC Analyses Coordinate Coordinate Pressure principalcomponents Flow principal components Beat principal components HCC X YP1 P2 P3 F1 F2 F3 B1 B2 B3 Patient Code 55 −0.405 −0.032 0.932 −0.0560.016 0.205 0.376 0.081 −0.01 −0.011 0.001 56 −0.39 −0.024 0.888 −0.0410.094 0.124 0.337 0.012 0.002 0.004 −0.001 59 −0.418 −0.021 0.899 0.0660.069 0.214 0.125 0.291 −0.003 0.002 −0.012 60 −0.411 −0.02 0.834 0.0580.031 0.249 0.326 −0.007 −0.002 −0.002 −0.001 62 −0.377 −0.017 0.870.044 0.139 0.211 0.309 −0.029 −0.009 −0.002 0.003 77 −0.388 −0.0060.781 −0.115 0.036 0.119 0.344 0.019 −0.002 −0.002 0 78 −0.39 −0.0150.869 −0.075 −0.006 0.194 0.385 0.141 0.004 0.002 0 82 −0.348 −0.0250.986 0.099 0.09 0.391 0.091 0.611 0.001 0 0 Breast Cancer 39 0.327−0.033 0.804 −0.007 0.044 0.172 0.337 0.044 −0.001 −0.001 0 41 0.327−0.034 0.838 −0.038 0.091 0.239 0.369 −0.002 0.001 0.002 0.001 42 0.316−0.014 0.116 0.067 0.752 0.027 0.318 0.116 0 0.002 −0.001 45 0.296−0.033 0.853 0.103 0.054 0.266 0.088 0.318 −0.008 0.002 0.004 46 0.292−0.024 0.683 0.057 −0.049 0.127 0.001 0.323 −0.003 −0.018 −0.023 470.285 −0.021 0.838 0.062 −0.221 0.193 0.034 0.324 0.015 −0.014 0.059 480.299 −0.025 0.862 0.086 −0.134 0.189 0.046 0.349 0.001 0 0 49 0.324−0.032 0.849 −0.069 0.066 0.225 0.378 0.047 0 0.002 0.001 HealthyIndividuals 4 −0.275 0.002 0.231 0.815 −0.01 0.054 0.099 0.337 −0.0010.006 −0.003 7 −0.284 0.037 0.852 0.257 −0.089 0.154 0.148 0.342 0.009 00 12 −0.255 0.043 0.351 0.211 0.507 0.278 −0.258 0.126 −0.003 −0.008−0.001 13 −0.32 0.052 0.917 0.005 0.024 0.251 0.382 0.062 0.003 0.001 017 −0.591 0.015 0.731 −0.095 0.14 0.094 0.352 −0.029 −0.001 −0.002−0.001 23 −0.572 0.014 0.872 0.195 −0.035 0.213 0.234 0.374 −0.009 0.003−0.015 75 −0.341 0.003 0.193 0.807 −0.222 0.197 0.141 0.287 0.002 0.070.027 79 −0.344 0.007 0.256 0.72 −0.014 −0.042 0.151 0.346 −0.002 0.0190.003

TABLE 3 Diagnosis based on hemodynamic parameter (Hdp), lineardiscriminant and geometry analyses d_group Cancer Healthy Cancer 0120.49729 Healthy 120.49729 0 LDA constant −0.89418 −68.98654 Area oftriangle 0.0171 0.33941 Apotema P-B −0.15385 −3.18876 Apotema P-F0.40858 2.7007 Apotema F-B −0.00324 0.65841 Area of circle −0.001−0.0002086 d_group HCC Breast Healthy HCC 0 0.96372 119.23965 Breast0.96372 0 118.8079 Healthy 119.23965 118.8079 0 LDA constant −1.56828−0.58072 −68.04536 Area of triangle 0.0159 0.01738 0.33439 Apotema P-B−0.07174 −0.19523 −3.12901 Apotema P-F 0.4447 0.37987 2.66957 ApotemaF-B 0.03225 −0.02252 0.6553 Area of circle −0.00176 −0.0005698−0.0003422

TABLE 4 Determination of four distinct hemodynamic patterns and theircorrelation in patients with diagnosis of cancer and without cancer inthe Discovery Group. Male Female Healthy Breast Healthy Correlation HCCControl cancer Control with Diagnosis (%) (%) (%) (%) Total Correctcorrelation 5 (83.3) 3 (100.0) 5 (83.3) 3 (100.0) 16 Wrong correlation 1(16.7) 0 1 (16.7) 0 2 total 6 3 6 3 18

TABLE 5 Identification of cancer specific hemodynamic response patternupon exposure to AM RF EMF modulated at specific and non−specificfrequencies in patients with diagnosis of cancer in the Discovery Group.HCC Breast cancer Cancer-specific Cancer-specific Non-cancer specificCancer-specific Non-cancer specific Hemodynamic frequencies frequenciesTotal frequencies frequencies Total response pattern # exposures (%) #exposures (%) Exposures # exposures (%) # exposures (%) Exposures Cancerspecific pattern 6 (100.0) 0 6 5 (83.3) 1 (14.3) 6 Non-cancer pattern 012 (100.0) 12 1 (16.7) 11 (91.6)  12 Total exposures 6 (100.0) 12(100.0) 18 6 (100)  12 (100.0) 18

TABLE 6 Determination of four distinct hemodynamic patterns and theircorrelation in patients with diagnosis of cancer and without cancer inthe Validation Group. Male Female Healthy Breast Healthy Correlation HCCControl cancer Control with Diagnosis (%) (%) (%) (%) Total Correct 11(100.0) 9 (69.2) 14 (100.0) 17 (94.4) 51 correlation Wrong 0 4 (30.8) 01 (5.6) 5 correlation total 11 (100.0) 13 (100.0) 14 (100.0)  18 (100.0)56 Sensitivity  100%  100% Specificity 69.2% 94.4%

TABLE 7 Identification of cancer specific hemodynamic response patternupon exposure to AM RF EMF modulated at specific and non−specificfrequencies in patients with diagnosis of cancer in the ValidationGroup. HCC Breast cancer Cancer-specific Cancer-specific Non-cancerspecific Cancer-specific Non-cancer specific Hemodynamic frequenciesfrequencies Total frequencies frequencies Total response pattern #exposures (%) # exposures (%) Exposures # exposures (%) # exposures (%)Exposures Cancer specific pattern 6 (100.0) 0 6 5 (83.3) 1 (14.3) 6Non-cancer pattern 0 12 (100.0) 12 1 (16.7) 11 (91.6)  12 Totalexposures 6 (100.0) 12 (100.0) 18 6 (100)  12 (100.0) 18

TABLE 8 Determination of four distinct hemodynamic patterns and theircorrelation with diagnosis and determination of cancer specifichemodynamic response pattern upon exposure to AM RF EMF modulated atspecific and non-specific frequencies in male and female patientsdiagnosed with HCC. Correlation with Diagnosis HCC (%) Male Female TotalCorrect correlation 6 (75.0) 5 1 6 Wrong correlation 2 (25.0) 1 1 2total  8 (100.0) 6 2 8 Male Female Cancer-specific Cancer-specificCancer-specific Cancer-specific Hemodynamic frequencies frequenciesfrequencies Total response pattern # exposures (%) # exposures #exposures # exposures Cancer specific pattern 8 (100.0) 6 2 8 Non-cancerpattern 0 0 0 0 Total exposures 8 (100.0) 6 2 8

What is claimed is:
 1. A hemodynamic parameter (Hdp) monitoring systemfor diagnosing a health condition of a patient, comprising: an Hdpmonitor that senses and measures, and including recording means forrecording at least the following listed Hdp values exhibited by thepatient during a basal or non-exposure period and furthermore Hdp valuesexhibited by the patient during or after an exposure period during whichthe patient is exposed to low-energy electromagnetic output signals:systolic blood pressure, diastolic blood pressure, median bloodpressure, stroke volume, cardiac output, total peripheral resistance, RRinterval, heart rate, and pulse pressure; and an electrically-poweredgenerator adapted to be actuated to generate said low-energyelectromagnetic carrier output signals for exposing or applying to thepatient such output signals during said exposure period.
 2. An Hdpmonitoring system according to claim 1, in which said Hdp monitor isadapted to sense and measure each of said Hdp values and separatelyrecord such Hdp values exhibited by the patient during both said basalor non-exposure period and said Hdp values exhibited by the patientduring or after said exposure period.
 3. An Hdp monitoring systemaccording to claim 1, in which the Hdp monitor is adapted to repeatedlysense and measure said Hdp values and record such values during a periodof time determined by at least ten heart-beat times.
 4. An Hdpmonitoring system according to any one of claim 1 3, in which theelectrically-powered generator includes amplitude modulation controlmeans for controlling the amplitude of the low energy electromagneticoutput signals and amplitude modulation (AM) frequency storage meanscomprising stored AM frequency values at which AM modulated outputsignals are generated.
 5. An Hdp monitoring system according to claim 4,in which the AM frequency storage means comprises AM frequency valuesdetermined to provide the AM modulated output signals with alleviationor curative effects on patients with a poor health condition.
 6. An Hdpmonitoring system according to claim 5, in which the specified poorhealth condition is a type or form of cancer.
 7. An Hdp monitoringsystem according to claim 6, in which the type or form of cancer ishepatocellular carcinoma (HCC) or breast cancer.
 8. A hemodynamicparameter (Hdp) monitoring system for establishing Hdp marker values orHdp surrogate marker values for purposes of comparison with Hdp valuesof the patient recorded by a recorder means of a Hdp monitoring system,comprising: an Hdp monitor that senses and measures, and includingrecording means for recording at least the following listed Hdp valuesexhibited by one or a plurality of surrogate patients during a basal ornon-exposure period and furthermore Hdp values exhibited by surrogatepatients during or after an exposure period during which the surrogatepatients are exposed to low-energy electromagnetic output signals:systolic blood pressure, diastolic blood pressure, median bloodpressure, stroke volume, cardiac output, total peripheral resistance, RRinterval, heart rate, and pulse pressure; and an electrically-poweredgenerator adapted to be actuated to generate said low-energyelectromagnetic carrier output signals for exposing or applying to thesurrogate patients such output signals during said exposure period. 9.An Hdp monitoring system according to claim 8, in which said Hdp monitoris adapted to sense and measure each of said Hdp values and separatelyrecord such Hdp values exhibited by surrogate patients during both saidbasal or non-exposure period and said Hdp values exhibited by surrogatepatients during or after said exposure period.
 10. An Hdp monitoringsystem according to claim 8, in which the Hdp monitor is adapted torepeatedly sense and measure said Hdp values and record such valuesduring a period of time determined by at least ten heart-beat times. 11.An Hdp monitoring system according to any one of claim 8, in which theelectrically-powered generator includes amplitude modulation controlmeans for controlling the amplitude of the low energy electromagneticoutput signals and amplitude modulation (AM) frequency storage meanscomprising stored AM frequency values at which AM modulated outputsignals are generated.
 12. An Hdp monitoring system according to claim11, in which the AM frequency storage means comprises AM frequencyvalues determined to provide the AM modulated output signals withalleviation or curative effects on patients with a poor healthcondition.
 13. An Hdp monitoring system according to claim 12, in whichthe specified poor health condition is a type or form of cancer.
 14. AnHdp monitoring system according to claim 13, in which the type or formof cancer is hepatocellular carcinoma (HCC) or breast cancer.
 15. An Hdpmonitoring system according to claim 8, in which said recordings of Hdpvalues are subjected to real time analysis of such recordings by meansof an analyser component integrated with or coupled to said recordingmeans included in the Hdp monitor.
 16. An Hdp monitoring systemaccording to claim 8, in which said recordings of Hdp values aresubjected to analysis of such recordings by an analysis center providedwith information related to recordings of said Hdp values.
 17. An Hdpmonitoring system according to claim 15, in which said analysis includescalculating representative values for each of the recorded Hdp values,optionally making a determination of ratios between differentrepresentative Hdp values, and comparing either or both of suchrepresentative values or ratios, with predetermined representativevalues or ratios, predetermined in patients known to be healthy orpredetermined to be suffering from or likely to develop an identifiedpoor health condition, whereby calculated representative values forrecorded Hdp values or ratios which match with predeterminedrepresentative Hdp values or ratios, provide an indication of adiagnosis of a health condition of a patient.
 18. An Hdp monitoringsystem according to claim 17, in which the health condition of thepatient is suspected or known to involve a form of cancerous cell growthor a likelihood of such a form of cancerous cell growth developing in apatient.
 19. An Hdp monitoring system according to claim 18, in whichthe health condition of the patient is suspected or known to involve aform of cancerous cell growth which is hepatocellular carcinoma (HCC) orbreast cancer.
 20. A method of diagnosing a health condition of apatient, comprising the steps of sensing and measuring and recording bymeans of an Hdp monitoring system, at least the following Hdp valuesexhibited by a patient and by one or a plurality of surrogate patients:systolic blood pressure, diastolic blood pressure, median bloodpressure, stroke volume, cardiac output, total peripheral resistance, RRinterval, heart rate, and pulse pressure, causing Hdp influences on boththe patient and one or a plurality of surrogate patients by means ofexposure or application of Hdp value-influencing electromagnetic outputsignals to the patient and to one or a plurality of surrogate patientsduring an exposure period, recording each of the measured Hdp values foreach of said hemodynamic parameters, measured during a non-exposureperiod and during or after an exposure period of application of saidelectromagnetic output signals to the patient and to one or a pluralityof surrogate patients, analysing the various recorded measured Hdpvalues to obtain representative Hdp values for each of the recorded Hdpvalues recorded from the patient and from one or a plurality ofsurrogate patients optionally making a determination of ratios betweendifferent representative Hdp values for each of the patient and one or aplurality of surrogate patients, and comparing either or both of said ofrepresentative values or ratios of different representative values ofthe patient, with predetermined representative values or ratios of oneor a plurality of surrogate patients pre-diagnosed to be healthy or tobe in an identified pre-diagnosed poor health condition, wherebyrepresentative values for recorded Hdp values or ratios of the patientwhich match with predetermined representative Hdp values or ratios ofthe one or a plurality of surrogate patients provide a diagnosis of ahealth condition of the patient.